Temporal retinal transcriptome and systems biology analysis identifies key pathways and hub genes in Staphylococcus aureus endophthalmitis

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Rajamani, Deepa ^d   Singh, Pawan Kumar ^a,b   Rottmann, Bruce G ^b   Singh, Natasha ^d   Bhasin, Manoj K ^d,e   Kumar, Ashok ^a,b,c  

^a WAYNE STATE UNIVERSITY   (United States)

^b WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c WAYNE STATE UNIVERSITY   (United States)

^d BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CCAAT ENHANCER BINDING PROTEIN; CYTOKINE; DNA BINDING PROTEIN; NUPR1 PROTEIN, MOUSE; TLR2 PROTEIN, MOUSE; TOLL LIKE RECEPTOR 2; TRANSCRIPTOME; TUMOR PROTEIN;

ANIMAL; C57BL MOUSE; DEFICIENCY; DISEASE MODEL; ENDOPHTHALMITIS; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE ONTOLOGY; GENE REGULATORY NETWORK; GENETICS; HOST PATHOGEN INTERACTION; HUMAN; IMMUNOLOGY; KNOCKOUT MOUSE; MICROBIOLOGY; MOLECULAR GENETICS; MOUSE; PATHOGENICITY; PATHOLOGY; PHYSIOLOGY; PRINCIPAL COMPONENT ANALYSIS; RETINA; SIGNAL TRANSDUCTION; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS INFECTION; SYSTEMS BIOLOGY;

ANIMALS; CCAAT-ENHANCER-BINDING PROTEINS; CYTOKINES; DISEASE MODELS, ANIMAL; DNA-BINDING PROTEINS; ENDOPHTHALMITIS; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE ONTOLOGY; GENE REGULATORY NETWORKS; HOST-PATHOGEN INTERACTIONS; HUMANS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MOLECULAR SEQUENCE ANNOTATION; NEOPLASM PROTEINS; PRINCIPAL COMPONENT ANALYSIS; RETINA; SIGNAL TRANSDUCTION; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; SYSTEMS BIOLOGY; TOLL-LIKE RECEPTOR 2; TRANSCRIPTOME;

EID: 84958581231     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep21502     Document Type: Article

References (78)

1. Chiquet, C. et al. Eubacterial PCR for bacterial detection and identification in 100 acute postcataract surgery endophthalmitis. Invest Ophthalmol Vis Sci 49, 1971-1978 (2008).
2. Kumar, A., Pandey, R. K., Miller, L. J., Singh, P. K. & Kanwar, M. Muller glia in retinal innate immunity: a perspective on their roles in endophthalmitis. Crit Rev Immunol 33, 119-135 (2013).
3. Singh, P. K., Donovan, D. M. & Kumar, A. Intravitreal Injection of the Chimeric Phage Endolysin Ply187 Protects Mice from Staphylococcus aureus Endophthalmitis. Antimicrob Agents Chemother 58, 4621-4629 (2014).
4. Hughes, D. S. & Hill, R. J. Infectious endophthalmitis after cataract surgery. Br J Ophthalmol 78, 227-232 (1994).
5. Dave, V. P., Pathengay, A., Schwartz, S. G. & Flynn, H. W. Jr. Endophthalmitis following pars plana vitrectomy: a literature review of incidence, causative organisms, and treatment outcomes. Clin Ophthalmol 8, 2183-2188 (2014).
6. Lawless, M. & Hodge, C. Global Implications of Refractive Laser Assisted Cataract Surgery (ReLACS). in Textbook of Refractive Laser Assisted Cataract Surgery (ReLACS) (eds. Krueger, R. R., Talamo, J. H. & Lindstrom, R. L.) 189-198 (Springer New York, 2013).
7. Brian, G. & Taylor, H. Cataract blindness-challenges for the 21st century. Bull World Health Organ 79, 249-256 (2001).
8. Campbell, R. J. et al. Rapid expansion of intravitreal drug injection procedures, 2000 to 2008: a population-based analysis. Arch Ophthalmol 128, 359-362 (2010).
9. Sadaka, A., Durand, M. L. & Gilmore, M. S. Bacterial endophthalmitis in the age of outpatient intravitreal therapies and cataract surgeries: Host-microbe interactions in intraocular infection. Prog Retin Eye Res 31, 316-331 (2012).
10. Gregory, M., Callegan, M. C. & Gilmore, M. S. Role of bacterial and host factors in infectious endophthalmitis. Chem Immunol Allergy 92, 266-275 (2007).
11. Callegan, M. C. et al. Bacterial endophthalmitis: therapeutic challenges and host-pathogen interactions. Prog Retin Eye Res 26, 189-203 (2007).
12. Petropoulos, I. K. et al. Expression of TNF-alpha, IL-1beta, and IFN-gamma in Staphylococcus epidermidis slime-positive experimental endophthalmitis is closely related to clinical inflammatory scores. Graefes Arch Clin Exp Ophthalmol 244, 1322-1328 (2006).
13. Ermis, S. S., Cetinkaya, Z., Kiyici, H. & Ozturk, F. Treatment of Staphylococcus epidermidis endophthalmitis with intravitreal moxifloxacin in a rabbit model. Tohoku J Exp Med 205, 223-229 (2005).
14. Ravindranath, R. M., Hasan, S. A. & Mondino, B. J. Immunopathologic features of Staphylococcus epidermidis-induced endophthalmitis in the rat. Curr Eye Res 16, 1036-1043 (1997).
15. Ramadan, R. T., Ramirez, R., Novosad, B. D. & Callegan, M. C. Acute inflammation and loss of retinal architecture and function during experimental Bacillus endophthalmitis. Curr Eye Res 31, 955-965 (2006).
16. Moyer, A. L., Ramadan, R. T., Novosad, B. D., Astley, R. & Callegan, M. C. Bacillus cereus-induced permeability of the blood-ocular barrier during experimental endophthalmitis. Invest Ophthalmol Vis Sci 50, 3783-3793 (2009).
17. Wiskur, B. J., Robinson, M. L., Farrand, A. J., Novosad, B. D. & Callegan, M. C. Toward improving therapeutic regimens for Bacillus endophthalmitis. Invest Ophthalmol Vis Sci 49, 1480-1487 (2008).
18. Callegan, M. C., Kane, S. T., Cochran, D. C. & Gilmore, M. S. Molecular mechanisms of Bacillus endophthalmitis pathogenesis. DNA Cell Biol 21, 367-373 (2002).
19. Kochan, T., Singla, A., Tosi, J. & Kumar, A. Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus. Infect Immun 80, 2076-2088 (2012).
20. Kumar, A., Singh, C. N., Glybina, I. V., Mahmoud, T. H. & Yu, F. S. Toll-like receptor 2 ligand-induced protection against bacterial endophthalmitis. J Infect Dis 201, 255-263 (2010).
21. Whiston, E. A. et al. alphaB-crystallin protects retinal tissue during Staphylococcus aureus-induced endophthalmitis. Infect Immun 76, 1781-1790 (2008).
22. Engelbert, M. & Gilmore, M. S. Fas ligand but not complement is critical for control of experimental Staphylococcus aureus Endophthalmitis. Invest Ophthalmol Vis Sci 46, 2479-2486 (2005).
23. Sugi, N., Whiston, E. A., Ksander, B. R. & Gregory, M. S. Increased resistance to Staphylococcus aureus endophthalmitis in BALB/c mice: Fas ligand is required for resolution of inflammation but not for bacterial clearance. Infect Immun 81, 2217-2225 (2013).
24. Akira, S., Uematsu, S. & Takeuchi, O. Pathogen recognition and innate immunity. Cell 124, 783-801 (2006).
25. Pasare, C. & Medzhitov, R. Toll-like receptors: linking innate and adaptive immunity. Microbes Infect 6, 1382-1387 (2004).
26. Pandey, R. K., Yu, F. S. & Kumar, A. Targeting toll-like receptor signaling as a novel approach to prevent ocular infectious diseases. Indian J Med Res 138, 609-619 (2013).
27. Kumar, A. & Yu, F. S. Toll-like receptors and corneal innate immunity. Curr Mol Med 6, 327-337 (2006).
28. Parkunan, S. M., Astley, R. & Callegan, M. C. Role of TLR5 and flagella in bacillus intraocular infection. PLoS One 9, e100543 (2014).
29. Hunt, J. J., Astley, R., Wheatley, N., Wang, J. T. & Callegan, M. C. TLR4 Contributes to the Host Response to Klebsiella Intraocular Infection. Curr Eye Res 39, 790-802 (2014).
30. Novosad, B. D., Astley, R. A. & Callegan, M. C. Role of Toll-like receptor (TLR) 2 in experimental Bacillus cereus endophthalmitis. PLoS One 6, e28619 (2011).
31. Kumar, A. & Shamsuddin, N. Retinal Muller glia initiate innate response to infectious stimuli via toll-like receptor signaling. PLoS One 7, e29830 (2012).
32. Shamsuddin, N. & Kumar, A. TLR2 mediates the innate response of retinal Muller glia to Staphylococcus aureus. J Immunol 186, 7089-7097 (2011).
33. Singh, P., Shiha, M. & Kumar, A. Antibacterial responses of retinal Muller glia: production of antimicrobial peptides, oxidative burst and phagocytosis. J Neuroinflammation 11, 33 (2014).
34. Tamayo, P. et al. Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation. Proc Natl Acad Sci USA 96, 2907-2912 (1999).
35. Talreja, D., Kaye, K. S., Yu, F. S., Walia, S. K. & Kumar, A. Pathogenicity of ocular isolates of Acinetobacter baumannii in a mouse model of bacterial endophthalmitis. Invest Ophthalmol Vis Sci 55, 2392-2402 (2014).
36. Callegan, M. et al. Bacterial endophthalmitis: therapeutic challenges and host-pathogen interactions. Prog Retin Eye Res 26, 189-203 (2007).
37. Kumar, A. & Shamsuddin, N. Retinal Muller glia initiate innate response to infectious stimuli via toll-like receptor signaling. PLoS One 7, e29830 (2012).
38. Ashida, H., Kim, M. & Sasakawa, C. Exploitation of the host ubiquitin system by human bacterial pathogens. Nat Rev Micro 12, 399-413 (2014).
39. Jiang, X. & Chen, Z. J. The role of ubiquitylation in immune defence and pathogen evasion. Nat Rev Immunol 12, 35-48 (2012).
40. Tanner, K., Brzovic, P. & Rohde, J. R. The bacterial pathogen-ubiquitin interface: lessons learned from Shigella. Cell Microbiol 17, 35-44 (2015).
41. Talreja, D., Singh, P. K. & Kumar, A. In Vivo Role of TLR2 and MyD88 Signaling in Eliciting Innate Immune Responses in Staphylococcal Endophthalmitis. Invest Ophthalmol Vis Sci 56, 1719-1732 (2015).
42. Parkunan, S. M. et al. Unexpected Roles for Toll-Like Receptor 4 and TRIF in Intraocular Infection with Gram-Positive Bacteria. Infect Immun 83, 3926-3936 (2015).
43. Hunt, J. J., Astley, R., Wheatley, N., Wang, J.-T. & Callegan, M. C. TLR4 Contributes to the Host Response to Klebsiella Intraocular Infection. Current Eye Research 39, 790-802 (2014).
44. Cho, J. S. et al. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest 120, 1762-1773 (2010).
45. Minegishi, Y. et al. Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome. J Exp Med 206, 1291-1301 (2009).
46. Taylor, P. R. et al. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, ROR[gamma]t and dectin-2. Nat Immunol 15, 143-151 (2014).
47. Karthikeyan, R. S. et al. Interleukin 17 Expression in Peripheral Blood Neutrophils From Fungal Keratitis Patients and Healthy Cohorts in Southern India. J Infect Dis 211, 130-134 (2015).
48. Heimer, S. R., Yamada, A., Russell, H. & Gilmore, M. Response of corneal epithelial cells to Staphylococcus aureus. Virulence 1, 223-235 (2010).
49. Walch-Rückheim, B. et al. Stromal Fibroblasts Induce CCL20 through IL6/C/EBPβ to Support the Recruitment of Th17 Cells during Cervical Cancer Progression. Cancer Res 75, 5248-5259 (2015).
50. Stark, George R. & Darnell Jr, James E. The JAK-STAT Pathway at Twenty. Immunity 36, 503-514 (2012).
51. Villarino, A. V., Kanno, Y., Ferdinand, J. R. & O'Shea, J. J. Mechanisms of Jak/STAT Signaling in Immunity and Disease. J Immunol 194, 21-27 (2015).
52. Tseng, W. P., Su, C. M. & Tang, C. H. FAK activation is required for TNF-alpha-induced IL-6 production in myoblasts. J Cell Physiol 223, 389-396 (2010).
53. Takeda, K. et al. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci USA 94, 3801-3804 (1997).
54. Yang, X. O. et al. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282, 9358-9363 (2007).
55. Yu, H., Lee, H., Herrmann, A., Buettner, R. & Jove, R. Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat Rev Cancer 14, 736-746 (2014).
56. Yu, H., Pardoll, D. & Jove, R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 9, 798-809 (2009).
57. Ernst, M., Thiem, S., Nguyen, P. M., Eissmann, M. & Putoczki, T. L. Epithelial gp130/Stat3 functions: an intestinal signaling node in health and disease. Semin Immunol 26, 29-37 (2014).
58. Jarnicki, A., Putoczki, T. & Ernst, M. Stat3: linking inflammation to epithelial cancer-more than a "gut" feeling? Cell Div 5, 14 (2010).
59. O'Shea, J. J. & Plenge, R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 36, 542-550 (2012).
60. O'Shea, J. J., Holland, S. M. & Staudt, L. M. JAKs and STATs in Immunity, Immunodeficiency, and Cancer. N Engl J Med 368, 161-170 (2013).
61. Ejarque-Ortiz, A., Tusell, J. M., Serratosa, J. & Saura, J. CCAAT/enhancer binding protein-alpha is down-regulated by toll-like receptor agonists in microglial cells. J Neurosci Res 85, 985-993 (2007).
62. Miller, M., Shuman, J. D., Sebastian, T., Dauter, Z. & Johnson, P. F. Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha. J Biol Chem 278, 15178-15184 (2003).
63. Davydov, I. V., Krammer, P. H. & Li-Weber, M. Nuclear factor-IL6 activates the human IL-4 promoter in T cells. J Immunol 155, 5273-5279 (1995).
64. van Dijk, T. B. et al. A composite C/EBP binding site is essential for the activity of the promoter of the IL-3/IL-5/granulocyte-macrophage colony-stimulating factor receptor beta c gene. J Immunol 163, 2674-2680 (1999).
65. Natsuka, S. et al. Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6. Blood 79, 460-466 (1992).
66. Greenwel, P. et al. Tumor necrosis factor alpha inhibits type I collagen synthesis through repressive CCAAT/enhancer-binding proteins. Mol Cell Biol 20, 912-918 (2000).
67. Wang, K. X. & Denhardt, D. T. Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev 19, 333-345 (2008).
68. Koh, A. et al. Role of osteopontin in neutrophil function. Immunology 122, 466-475 (2007).
69. Stanley, E. R. et al. Biology and action of colony-stimulating factor-1. Mol Reprod Dev 46, 4-10 (1997).
70. Nemunaitis, J. Macrophage function activating cytokines: potential clinical application. Crit Rev Oncol Hematol 14, 153-171 (1993).
71. Sims, J. E. & Smith, D. E. The IL-1 family: regulators of immunity. Nat Rev Immunol 10, 89-102 (2010).
72. Dinarello, C. A. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27, 519-550 (2009).
73. Rathinam, V. A. K., Vanaja, S. K. & Fitzgerald, K. A. Regulation of inflammasome signaling. Nat Immunol 13, 333-332 (2012).
74. Irizarry, R. A. et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4, 249-264 (2003).
75. Koulmanda, M. et al. Curative and beta cell regenerative effects of alpha1-antitrypsin treatment in autoimmune diabetic NOD mice. Proc Natl Acad Sci USA 105, 16242-16247 (2008).
76. Damrauer, S. M. et al. A20 modulates lipid metabolism and energy production to promote liver regeneration. PLoS One 6, e17715 (2011).
77. Bhasin, M. K. et al. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways. PLoS One 8, e62817 (2013).
78. Huang da, W. et al. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res 35, W169-175 (2007).